Ophthalmic drug delivery system using polymer micelle

Abstract

The current situation is such that it is difficult for drugs to reach posterior tissues of an eyeball, such as choroid and retina, with the result that treating diseases in such regions is difficult. Thus, how to attain effective delivery of drugs is of importance. It has been found that effective delivery of drugs to positerior tissues of the eyeball, such as choroid and retina, especially those wherein vascularization has occurred can be accomplished by systemic administration, especially intravenous administration of polymer micells having a drug incorporated therein. Further, it has been found that when a photosensitive substance is used as a drug and PDT is carried out, choroidal neo-vessels can be effectively choked so as to be useful for the treatment of age-related macular degeneration.

Description

TECHNICAL FIELD [0001] The present invention relates to an ophthalmic drug delivery system characterized by efficiently delivering a drug to posterior tissues of an eyeball such as choroid and retina, especially those wherein neovascularization has occured, by administering a polymer micelle having a drug incorporated therein that is useful as a therapeutic drug for an ocular disease. The drug delivery system of the invention can be effectively applied to photodynamic therapies when a photosensitive substance is used as the drug, and can be subjected to therapy for age-related macular degeneration or the like through occluding choroidal new vessels. BACKGROUND ART [0002] Polymer micelles are nanoparticles fundamentally formed with a hydrophilic polymer chain as a shell and a hydrophobic polymer chain as a core. Various studies have been made on the polymer micelles for drug solubilization or as a carrier for drug delivery. Examples of the studies involve: a report on a carrier for r...

AI Technical Summary

Benefits of technology

[0025] Advantage of the invention will be described in detail in the section of Example, in which intraocular transfer of a polymer micelle was investigated when a fluorescence-lebelled polymer micelle was systemically administered (intravenous injection) to a rat choroidal neovascular (CNV) model. Consequently, accumulation of intense fluorescence agreeing with choriocapillaris vascular lamina and CNV was found one hour after the administration. Twenty four hours after the administration, fluorescence in normal choriocapillaris vascular lamina was attenuated, however, accumulation of intense fluorescence agreeing with CNV remained. In other words, it was revealed that the polymer micelle exhibits high accumulating capability for CNV, and is effective as a DDS for CNV.

[0026] In addition, when a photosensitive substance is used as a drug, it can be effectively used in therapy for AMD. The photosensitive substance is not particularly limited, but porphrin derivatives presented in the section of Background art are preferred, and illustrative examples thereof include dendrimer-type porphyrin, verteporfin, SnET2, ATX-S10, MV6401, temoporfin, talaporfin and the like. In particular, dendrimer-type porphyrin is preferred.

[0027] When the polymer micelle is used as a carrier for the photosensitive substance, the photosensitive substance can be stabilized, and as is also clear from the Examples below, it can be efficaciously accumulated to CNV. Thus, efficacious occlusion of new vessels are enabled even at a low dose of laser. Therefore, less influence is exerted on ocular tissues, and continuous repetition of therapy for a long period of time is enabled, also leading to expectation to complete recovery of AMD.

[0028] Furthermore, many of photosensitive substances used in the PDT are slightly soluble in water; therefore, attempts have been made such as formation of a liposome preparation or the like to execute administration. However, in this instance, the preparation may be necessarily administered intravenously for a long period of time at regular intervals, thereby increasing burdens to the patients. When the polymer micelle is used, the photosensitive substance can be solubilized in water, therefore, administration by usual intravenous injection is enabled to eliminate the aforementioned burdens to the patients.

[0029] Furthermore, the PDT may also involve problems of light-sensitive disorder of skin. When the dendrimer-type porphyrin is used as the photosensitive substance, light-sensitive disorder is hardly found, suggesting an excellent characteristic of the dendrimer-type porphyrin.

Problems solved by technology

However, the drug hardly reaches posterior tissues of eyeball such as choroid and retina in administration of eye drops, therefore, therapy for diseases in such sites has been difficult under the current situations.

Thus, there has been a problem on how a drug is efficiently delivered to a posterior tissue of an eyeball.

Furthermore, many diseases of a posterior segment of an eyeball are intractable.

Particularly, exudative AMD is a disease that causes severe visual loss, and therapy thereof is very difficult.

Because irradiation of a laser beam may affect ocular tissues, continuous repetition of irradiation is difficult in the prior art.

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